Pharmacokinetics of Voxilaprevir in Adults With Normal Hepatic Function and Moderate or Severe Hepatic Impairment

A Phase 1 Open-Label, Parallel-Group, Single-Dose Study to Evaluate the Pharmacokinetics of GS-9857 in Subjects With Normal Hepatic Function and Moderate or Severe Hepatic Impairment

The primary objective of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of a single dose of voxilaprevir (formerly GS-9857) in participants with normal hepatic function, moderate hepatic impairment and severe hepatic impairment. Participants in the healthy control group will be matched to participants with impaired hepatic function by gender, age (± 10 years), and body mass index (± 15%).

Study Overview

• Status: Completed
• Conditions: HCV Infection
• Intervention / Treatment: Drug: Voxilaprevir

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • München, Germany, 81241
    • APEX GmbH
• New Zealand
  • Auckland, New Zealand, 1142
    • Auckland Clinical Studies
• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• All individuals:

  • Screening laboratory values within defined thresholds for group
  • Use of two effective contraception methods if female of childbearing potential or sexually active male

• For individuals with moderate hepatic impairment:

  • Diagnosis of chronic (> 6 months) hepatic impairment
  • Score on the Child-Pugh-Turcotte (CPT) scale of 7-9 at screening (Child Pugh Class B).

• For individuals with severe hepatic impairment:

  • Diagnosis of chronic (> 6 months) hepatic impairment
  • Score on the CPT scale of 10-15 at screening (Child Pugh Class C)

• For individuals with normal hepatic function:

  • Hepatitis C Virus (HCV) antibody and hepatitis B surface antigen negative

Key Exclusion Criteria:

• All individuals:

  • Pregnant or nursing female or male with pregnant female partner
  • HIV infection
  • History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol

• For individuals with moderate or severe hepatic impairment:

  • Active HCV infection
  • Current hepatic encephalopathy
  • Variceal bleeding in the last 6 months unless banded
  • Prior placement of a portosystemic shunt
  • History of hepatorenal or hepatopulmonary syndrome
  • Spontaneous bacterial peritonitis currently or within the last 6 months
  • Hospitalization within the last 2 months related to cirrhosis
  • Confirmed hypotension
  • Suspicion of hepatocellular carcinoma

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Hepatic Impaired; Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1.	Drug: Voxilaprevir; 100 mg tablet administered orally; Other Names: GS-9857
Experimental: Severe Hepatic Impaired; Participants with severe hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1.	Drug: Voxilaprevir; 100 mg tablet administered orally; Other Names: GS-9857

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameter of Voxilaprevir: AUCinf	AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. Data presented are unadjusted geometric means and confidence intervals.	0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose
Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast	AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. Data presented are unadjusted geometric means and confidence intervals.	0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours post-dose
PK Parameter of Voxilaprevir: Cmax	Cmax is defined as the maximum observed plasma concentration of drug.Data presented are unadjusted geometric means and confidence intervals.	0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Lawitz E, Marbury T, Kirby BJ, Au NT, Mathias A, Stamm LM, et al. The Effect of Renal or Hepatic Impairment on the Pharmacokinetics of GS-9857, A Pan-Genotypic HCV NS3/4A Protease Inhibitor [Abstract FRI-167]. J Hepatology 2016:S613-S4.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2015
• Primary Completion (Actual): March 4, 2016
• Study Completion (Actual): March 4, 2016

Study Registration Dates

• First Submitted: March 20, 2015
• First Submitted That Met QC Criteria: March 20, 2015
• First Posted (Estimate): March 25, 2015

Study Record Updates

• Last Update Posted (Actual): April 9, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C
• Other Study ID Numbers: GS-US-338-1126; 2015-000342-30 (EudraCT Number)